Early-life oral nitrate-reducing bacteria and cardiovascular risk in young children

Objectives: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Besides the conventional CVD risk factors, studies in adults have shown levels of oral nitrate-reducing bacteria (NRB) to be inversely associated with blood pressure. Evidence shows initiation of subclinical hypertension and atherosclerosis to occur as early as in childhood, emphasizing the need for early identification of CVD-susceptible individuals. Therefore, we aimed to test the potential link of early-life oral NRB with CVD risk markers in later childhood.
Methods: Data was obtained from Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. Oral microbiome samples from tooth and tongue dorsum of 323 children were collected at 2-, 3- and 5-years and characterized using 16S rRNA sequencing (Illumina HiSeq). NRB exposure was operationalised as ratio of NRB genera and Streptococcus (NRB/S ratio). Child’s systolic/diastolic blood pressure (SBP/DBP) was recorded annually from 3- to 8-years with measurement of CVD risk factors including arterial thickness (defined by carotid intima-media thickness, cIMT), aortic augmentation index (AIx) and pulse wave velocity (PWV) at 6-years. Linear mixed effect modelling was used to test association of NRB/S ratio with repeated measures of SBP/DBP. Linear regression was used to test association with cIMT/Alx/PWv at 6-years.
Results: After adjusting for potential confounders, multivariable analysis demonstrated an inverse relationship between NRB/S ratio in tongue dorsum at 5-years with cIMT at 6-years and SBP/DBP at 7- and 8-years (all p<0.05). This association was absent with NRBs from tooth surfaces. Oral NRB/S ratio at 5-years significantly improved prediction performance of core model for the outcome “elevated SBP (>90th percentile)” at 8-years, with increase in area under the curve from 0.71 to 0.84 (p<0.05).
Conclusions: Higher NRB levels in early life was associated with reduced blood pressure in later childhood, potentially mediated by lower carotid intima-media thickness. Site-specific NRB colonization may be a promising cardiovascular health predictor.